Homozygous sickle cell disease (HbSS) is characterized by increased hemolytic rate of "sickle shaped" erythrocytes. In addition, individuals with HbSS also have lower erythrocyte concentrations of the endogenously produced antioxidant glutathione (GSH), suggesting that they have impaired antioxidant capacity. It has been proposed that the generation of superoxide free radical by hemichromes, iron atoms and released haem groups, leads to peroxidation of the erythrocyte lipid membrane, which contributes to the sickling process. However, the extent to which antioxidant capacity is actually impaired, the mechanism(s) underlying such an impairment, and the relationships to oxidant damage and to the degree of in vivo sickling in HbSS have not been determined. The research proposed addresses the following hypotheses: i) HbSS subjects have lower erythrocyte GSH concentrations than control subjects because they synthesize GSH at a slower rate. ii) The slower rate of GSH synthesis is due to reduced availability of glycine and cysteine because of slower de novo synthesis of these two amino acids. iii) Supplementing the diets of the HbSS subjects with either cysteine, glycine, or cysteine plus glycine will stimulate GSH synthesis to a higher rate than its rate of consumption thereby replenishing the GSH pool size. iv) The higher oxidative load of the HbSS subject is directly related to the decreased synthesis and availability of GSH, hence stimulation of GSH synthesis rate will result in a decreased oxidative stress. Using biochemical and stable isotope tracer methods, these hypotheses will be tested in 32 subjects with HbSS and 8 control subjects matched for age, gender and usual dietary intakes. The experimental protocol will determine differences in 1) the rates of synthesis of erythrocyte GSH, cysteine and glycine, 2) whole body protein breakdown rate, 3) the plasma concentrations of lipid hydroperoxides, 4) the resistance of erythrocyte to oxidative stress at baseline and after a 4 weeks of dietary supplementation. The data obtained will provide insight into the relationship between oxidant capacity and sickling and whether dietary intervention can improve the metabolic status of subjects with HbSS.